Multiple myeloma (MM) is a plasma cell dyscrasia that accounts for almost 10% of all hematologic malignancies. Renal disease in myeloma most often presents as renal insufficiency and proteinuria. Occasionally patients with myeloma present with renal tubular dysfunction, including defects in acidification and concentration, and rarely with the Fanconi syndrome. The spectrum of renal lesions that is seen in patients with myeloma include “myeloma kidney,” or cast nephropathy; light chain (AL) amyloidosis; monoclonal Ig deposition disease (MIDD); and less frequently cryoglobulinemic glomerulonephritis and proliferative glomerulonephritis.
The renal pathology of cast nephropathy, MIDD and amyloidosis is diverse, but in each case the initial pathogeetic step is the production in the bone marrow of an abnormal immunoglobulin (Ig) fragment (usually an Ig light chain) by a clone of neoplastic plasma cells. During normal and neoplastic Ig synthesis plasma cells produce an excess of light chains that are released into the circulation. However, normal light chains are filtered by the glomeruli and are endocytosed and metabolized by the tubules without being deposited in the renal structures or causing pathology.
Recently, it was demonstrated that CKD-EPI equations based on Cystatin C (CysC) for the estimation of GFR detects more patients with stage 3–5 renal impairment than the MDRD or CKD-EPI equations based only in serum creatinine. Moreover, CKD-EPI-CysC was the only equation that could predict for overall survival, possibly due to the very strong correlation of CysC with International Staging System for Multiple Myeloma (ISS stage), as myeloma cells also produce CysC. Therefore the serum CysC level could reflect not only renal impairment but also tumor burden and prognosis in multiple myeloma. It seems as if increased CysC in blood as myeloma progressed was filtrated and excreted in excessive amounts. Furthermore, we have found that almost all newly diagnosed symptomatic MM patients have tubular damage as assessed by elevated urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), suggesting that renal impairment is present very early in the disease course.
Comparable results were also found in patients with asymptomatic MM and even in patients with Monoclonal Gammopathy of Undetermined Significance (MGUS), which is a premalignant plasma-cell proliferative disorder associated with a life-long risk of progression to MM. In patients with MGUS, high levels of urinary and serum NGAL indicate the presence of subclinical renal damage in these patients early in the course of their disease, when other markers of renal function, such as sCr or even the more sensitive CysC indicate that renal function is preserved. Measurement of urinary NGAL and serum CysC offers valuable information for the kidney function of MM patients, and their measurement may help in the identification of patients with high risk for the development of acute renal failure, as these two biomarkers correlated significantly with the involved serum free light chain. The value of Kidney Injury Molecule-1 (KIM-1) seems to be very low in myeloma, reflecting the differences in the pathogenesis of myeloma-related renal dysfunction rather than toxic acute renal injury of other etiology.
References:
1. Terpos et al. Eur J of Haematol 91:347–355, 2013.
2. Terpos and Papassotiriou unpublished data.